PHC62004

Basic Pharmacology and Toxicology with Health Informatics

Answer Sheet - Practical 1:

Computer Assisted Learning (CAL) -

Effects of Agonists on Guinea Pig Ileum
[9% of total marks (30%) for Practical component]

Name of student: Date: May 18 2020 Student ID number:

Part I: Concepts of Pharmacodynamics - Agonists

1. Define the terms in Table 1. (7 marks)

Table 1: Pharmacodynamic concepts for determining properties of drugs.
Term Definition
Affinity is a measurement on how tight and strong a drug binds or unite to its
a Affinity receptor. The smaller the Kd, the greater the affinity.

Efficacy describes biological response resulting from the drug-receptor interaction

b Efficacy between receptor occupancy and the ability to start a response. The maximum
response called Emax.
Agonist is ligands that bind and activate a receptor to generate a response and causes
c Agonist an action.

Antagonist is ligands that bind to a receptor without activating them, decline the
d Antagonist receptors ability and block agonist reaction.

Selectivity is the ability of analytical method to differentiate various

e Selectivity substances in the sample and is applicable to methods that have two or more
components separated and quantitated in a complex matrix.

Specificity is the ability of analytical method to search interest in the presence

f Specificity of the component. However, only a single parameter can be measured.

Potency illustrates the relationship between the dose of the drug and the
magnitude of the effect. The measurement of the dose (amount) required to
g Potency produce a specific effect on the body. High potent drug induces a strong effect
with a low drug concentration, while low potent drug gives the same response
at higher concentration.

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2. Discuss the difference between a full agonist, a partial agonist and an inverse agonist.
(4 marks)

Full agonist is substance or drug that bind to the receptors and produces a maximal response
Partial agonist has lower efficacy than full agonist, so it can never achieve the maximal
response
Same as before, inverse agonist is a ligand that binds to the receptors. However, it produces the
opposite of the effect to the normal expected effect of receptor activation, i.e. illustrates
negative efficacy.

3. List the FOUR (4) families of therapeutic exploitable pharmacologic receptors,

including the response time and ONE (1) example of receptor for each in Table 2.
Some columns have been filled as examples. (9 marks)

Table 2: The important therapeutic exploitable pharmacologic receptors.

Receptor family Response time Example of receptor
Rapid (within
a Ligand-gated ion channels miliseconds) Cholinergic nicotinic receptors

Transmembrane G protein-
b Rapid (within seconds) Alpha and beta adrenoceptors
coupled receptors

c Enzyme-linked receptors Slow (Hours) Insulin receptors

d Intracellular receptors Slow (hours) Steroid receptors

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Part II: OBSim Simulation - Data Interpretation and Discussion

NOTE: Attach all data tables (1 to 4) and the semi-log graphs plotted in this worksheet.

4. List the type of receptor(s) of the agonists addressed in this practical.

State ONE (1) clinical application for each agonist. (8 marks)

Table 3: Type of receptors and clinical application(s) of selected agonists.

Agonist Type of receptor(s) Application
Nicotinic to treat myasthenia gravis, and the
a Acetylcholine muscarinic symptoms of Alzheimer's disease

Nicotinic the treatment of glaucoma, but it is also

b Carbachol muscarinic used during ophthalmic surgery.

muscarinic to treat dry mouth caused by Sjogren's

syndrome or by radiation, to treat head and
neck cancer.
c Pilocarpine

G protein–coupled receptors regulating physiological function in the gut

and acting as a neurotransmitter for the
d Histamine brain, spinal cord, and uterus.

5. Muscarinic receptors and nicotinic receptors are the two main types of “cholinergic”
receptors. Discuss the physiological location (e.g. cell type, nerves etc) where these
receptors are mostly found. (2 marks)

Cholinergic plays an important role in memory, digestion, control of heartbeat, blood

pressure, movement and many other function.

Muscarinic Receptors are found on all parasympathetic nervous cells (cardia conduction
system, exocrine glands, smooth muscles) , some (generalized sweat glands) sympathetic
effector system and central nervous system.

Nicotinic Receptors are found in the skeletal neuromuscular juctions, sympathetic and
parasympathetic nervous system, autonomic ganglia, central nervous system.

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6. Based on your 1st semi-log graph:

a. Determine the EC50 value of : (4 marks)
i. Acetylcholine : 5 M
ii. Carbachol : 6 M
iii. Pilocarpine : 150 M
iv. Histamine : 20 M

b. Discuss how potency of a drug is determined and the relative potencies of the
muscarinic agonists used in this practical.
(3 marks)

Potency of a drug determined by calculating 50% of the concentration (EC50) or

dose (ED50) with graph, which the E max percentage as y-axis and drug
concentration as x-axis. The relative potencies of the muscarinic agonists obtained
on guinea-pig ileum are appreciably different. They are also appreciably larger than
the values. calculated from estimates of the semi-log EC50, Pilocarpine has the
largest concentration while acetylcholine has the smallest concentration. It makes
acetylcholine more potent than the other three agonists.

7. Based on your 2nd semi-log graph:

a. Discuss how efficacy of a drug is determined and the relative efficacies of the
muscarinic agonists used in this practical.

(3 marks)

The effect of the drug is illustrated in a graph, to give the dose–response curve. The
concentration of agonists used are displayed by the X axis and the half maximal
and maximal responses are displayed by the Y axis. The highest point on the curve
shows the maximum response (efficacy) and is referred to as the Emax. To get the
second semi-log graph, we were first comparing the maximum response of each
agonist. Pilocarpine has the highest response with 13.7. Then, we calculate the E
max normalized percentage. Based on the data, pilocarpine has the highest
efficacies with being the only one that reaches 100% while the other three agonist
are 98%.

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b. Explain why this evaluation (i.e. efficacy) provides important physiological information.
(2 marks)

efficacy provides important physiological information because it is the major

determinant of a drug. Calculating the efficacy let us know how much the
concentration of the drug to reach maximum response achievable from a drug and
reach the therapeutic index. This is one of ways to prevent overdose.

8. Potency vs. Efficacy. Discuss which one has more clinical importance and why.
(3 marks)

Efficacy has more clinical importance that potency.

Potency means measurement of the dose (amount) required to produce a certain effect.
Efficacy determines maximal response of a drug to achieve desired effect. It means how
well the drug does to your body. So, it does not matter how much the dose is required
because potency of the drug does not necessarily mean that it will have greater effect on
the body. The higher the efficacy, the higher the effectivity of the drug.

Total:

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Acetylcholine Maximum contractile force (gms)

Stock conc. Vol. to add to Final conc.

[nM]
[M] 10 mL organ 1 2 3 Average % Emax % Emax
bath (uL)
Normaliz Normalized (II)
ed (1)

0.00E+00 0 0 0 0 0 0 0 0

1.00E-08 1000 uL 1.0E-09 2.8041 2.716 2.7455 2.755 21 20

1.00E-07 300 uL 3E-09 5.999 5.4226 6.341 5.921 44 43

1.00E-07 900 uL 9E-09 9.6434 9.1774 9.9463 9.589 72 70

1.00E-06 270 uL 2.7E-08 11.93 11.666 12.233 11.943 90 88

1.00E-06 810 uL 8.1E-08 12.897 12.594 13.21 12.9 97 95

1.00E-05 243 uL 2.4E-07 13.395 12.965 13.122 13.161 99 97

1.00E-05 729 uL 7.2E-07 13.385 13.405 13.249 13.346 100 98

1.00E-04 218 uL 2.1E-06 13.569 13.229 13.415 13.404 100 98

1.00E-04 656 uL 6.5E-06 13.346 13.200 13.219 13.255 99 97

1.00E-03 196 uL 1.9E-05 13.366 13.337 13.366 13.356 100 98

1.00E-03 590 uL 5.9E-05 13.425 13.239 13.356 13.34 100 98

1.00E-02 177 uL 1.7E-04 13.581 13.102 13.249

1.00E-02 531 uL 5.3E-04 13.62 13.210 13.131

1.00E-01 159 uL 1.5E-03 13.532 13.278 13.288

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Carbachol Maximum contractile force (gms)

Stock Vol. to add to Final

conc. conc.
10 mL organ [nM] 1 2 3 Average % Emax % Emax
[M] bath (uL)
Normalized Normalized
(1) (II)

0.00E+00 0 0 0 0 0 0 0 0

1.00E-08 1000 uL 1.0E-09 2.257 2.4231 2.4035 2.361 18 17

1.00E-07 300 uL 3E-09 5.1979 5.276 5.1979 5.224 39 38

1.00E-07 900 uL 9E-09 8.9204 9.106 9.106 9.04 67 66

1.00E-06 270 uL 2.7E-08 11.578 11.519 11.91 11.669 87 86

1.00E-06 810 uL 8.1E-08 12.692 12.633 12.936 12.754 95 94

1.00E-05 243 uL 2.4E-07 13.405 13.200 13.454 13.353 100 98

1.00E-05 729 uL 7.2E-07 13.239 13.131 13.708 13.359 100 98

1.00E-04 218 uL 2.1E-06 13.258 13.268 13.776 13.434 100 99

1.00E-04 656 uL 6.5E-06 13.366 13.180 13.796 13.447 100 99

1.00E-03 196 uL 1.9E-05 13.395 13.161 13.727 13.328 99 98

1.00E-03 590 uL 5.9E-05 13.415 13.200 13.669 13.428 100 98

1.00E-02 177 uL 1.7E-04 13.483 13.151 13.62 13.418 100 98

1.00E-02 531 uL 5.3E-04 13.503 13.190 13.649 13.447

1.00E-01 159 uL 1.5E-03 13.542 13.229 13.718 13.496

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Pilocarpine Maximum contractile force (gms)

Stock conc. Vol. to add to Final conc.

[nM]
[M] 10 mL organ 1 2 3 Average % Emax % Emax
bath (uL)
Normalized Normalized
(1) (II)

0.00E+00 0 0 0 0 0 0 0 0

1.00E-08 1000 uL 1.0E-09 0.0195 0.1172 0.5862 0.241 2 2

4 2

1.00E-07 300 uL 3E-09 0.3321 0.1563 0.2442 0.244 2 2

9 6

1.00E-07 900 uL 9E-09 0.6839 0.5471 0.7230 0.651 5 5

3 1

1.00E-06 270 uL 2.7E-08 1.9638 0.6512 1.9052 1.507 11 11

1.00E-06 810 uL 8.1E-08 4.7093 4.426 4.2697 4.468 33 33

1.00E-05 243 uL 2.4E-07 8.7512 8.002 8.1094 8.288 61 61

1.00E-05 729 uL 7.2E-07 11.593 10.738 10.708 11.013 81 81

1.00E-04 218 uL 2.1E-06 12.975 12.008 12.428 12.47 91 91

1.00E-04 656 uL 6.5E-06 13.815 12.692 12.721 13.076 96 96

1.00E-03 196 uL 1.9E-05 13.884 12.868 13.141 13.298 98 98

1.00E-03 590 uL 5.9E-05 14.128 12.965 13.884 13.659 100 100

1.00E-02 177 uL 1.7E-04 14.167 13.141 13.874 13.727 100 100

1.00E-02 531 uL 5.3E-04 13.884 13.024 13.933 13.614 100 100

1.00E-01 159 uL 1.5E-03 14.157 12.926 13.825 13.636 100 100

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Histamine Maximum contractile force (gms)

Stock conc. Vol. to add to Final

conc.
[M] 10 mL organ [nM] 1 2 3 Average % Emax % Emax
bath (uL)
Normalized Normalized
(1) (II)

0.00E+00 0 0 0 0 0 0 0 0

1.00E-08 1000 uL 1.0E-09 0.6057 0.63508 0.5276 0.589 4 4

6

1.00E-07 300 uL 3E-09 1.9248 0.6317 1.7196 1.425 11 10

1.00E-07 900 uL 9E-09 4.3771 4.0938 4.3185 4.263 32 31

1.00E-06 270 uL 2.7E-08 8.0606 7.787 8.1485 7.999 60 59

1.00E-06 810 uL 8.1E-08 10.787 10.718 11.207 10.904 82 80

1.00E-05 243 uL 2.4E-07 12.396 12.203 12.897 12.499 94 92

1.00E-05 729 uL 7.2E-07 12.702 12.555 13.405 12.887 97 95

1.00E-04 218 uL 2.1E-06 12.956 12.858 13.708 13.174 99 97

1.00E-04 656 uL 6.5E-06 13.024 12.936 13.747 13.236 99 97

1.00E-03 196 uL 1.9E-05 13.436 12.946 13.923 13.435 100 99

1.00E-03 590 uL 5.9E-05 13.161 12.965 13.835 13.320 100 98

1.00E-02 177 uL 1.7E-04 13.268 13.063 13.874 13.402 100 98

1.00E-02 531 uL 5.3E-04 13.141 13.17 13.727 13.346 100 98

1.00E-01 159 uL 1.5E-03 13.229 12.995 13.854 13.359

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